1. Field of the Invention
This invention generally relates to a system and method for iontophoretic drug delivery having features for reducing irritation to the skin of an animal and more particularly to a system and method for delivery of power during iontophoretic drug delivery in a sequence for reducing skin irritation.
2. Description of the Prior Art
Iontophoresis is gaining increased acceptance as an effective method for application of ionic agents or ionic drugs through the skin of an animal. Iontophoresis can be defined as the electrically driven application of drugs or medications, in their ionic form, to the surface tissues of an animal. The application of electric current causes migration of ions into the tissue wherein such migration is proportional to the quantity of current applied through the iontophoretic system.
Skin irritation can occur during iontophoretic drug delivery. Efforts to minimize irritation have been directed to regulating the level of current, improving the electrical connection of the electrode with the skin and reducing the hydrolysis of water in the ionic medication. Irritation of the skin may be subjective wherein the iontophoretic electrode delivers so much power that it causes extreme discomfort to the patient. There are also objective indicia of irritation such as petechia, erythema and edema. Occurrence of such forms of irritation is discussed by Nancy A. Monteiro-Riviere in a paper presented in Fundamental Applied Technology, entitled "Altered Epidermal Morphology Secondary to Lidocaine Iontophoresis: In Vivo and In Vitro Studies in Procaine Skin", Vol. 15, pages 174-185 (1990).
It is known that the impedance of a patient's skin can range from over 100,000 ohms to nearly 1000 ohms, depending on the duration that the iontophoretic current is applied, the magnitude of the current which is being delivered, the location of the system on the patient's body, and other factors. In a system where the desired current level, which is determined in part by the drug administered to the patient, is one milliamp, a voltage potential of 100 volts would result if the skin impedance is 100,000 ohms. Since such a voltage would cause undesirable sensations to the user, it is highly desirable to limit the voltage across the electrodes of the iontophoretic drug delivery device to a more tolerable level.
Numerous prior art references attempt to teach iontophoretic devices which attempt to avoid irritation and/or tissue damage. For example, U.S. Pat. No. 4,292,968 to Ellis discloses an apparatus for delivering constant current during ion therapy (iontophoresis) which will abruptly switch to delivering constant voltage when the voltage across the electrodes reaches a predetermined level. Thus, the Ellis patent discloses a dual mode power source for an iontophoretic system.
However, the dual mode power source described in the Ellis patent is impractical for use with a transdermal drug delivery system. The Ellis power source employs a voltage limit of 1.1 volts. While skin impedance levels in man can range as low as 1,000 ohms, more typical values during drug delivery are in the range of 5,000-10,000 ohms. This leaves a current typically in the range of 100 to 200 .mu.A, a level which will fail to deliver much drug.
Also, the Ellis dual mode power source first provides a constant current to the electrodes of the drug delivery device, and then switches to a constant voltage if the voltage across the electrodes exceeds 1.1 volts. As described in the present invention, it is the opposite sequence, that is, changing from a constant voltage to a constant current, which is important in reducing skin irritation and burning.
U.S. Pat. No. 4,141,359 to Jacobsen et al. teaches an epidermal iontophoresis device which is capable of maintaining a constant current through the epidermal tissue. To prevent excessive voltage build-up and the accompanying dangers of shock and burns, a comparative circuit monitors current flow and voltage across the electrodes and automatically triggers an SCR shut down circuit when impedance readings are outside of predetermined limits.
The Jacobsen et al. patent thus describes an iontophoresis power source which is a constant current source with an output voltage capable of reaching 60 volts. There is no means to prevent the voltage from reaching this level which can cause adverse sensations to the patient. Described in this patent is a safety mechanism which is activated if the patch is removed while power is being delivered. This mechanism checks the impedance of the load and turns the system off if there is a large sudden change in the impedance.
As mentioned above, it is well known that undesirable sensations will arise when voltages of this level (60 volts) are applied to the skin. To avoid these sensations, the circuit described in the Jacobsen et al. patent provides for the user to set the level of controlled current, and in this way avoid the sensations. There is no provision for any automatic means to limit these sensations. Hence, by providing user control of the level of constant current, the Jacobsen et al. patent teaches away from the concept of a biphasic power source which utilizes the skin impedance to accomplish the phase transition.
Although the prior art is replete with devices for reducing skin irritation and skin damage, the prior art efforts appear to focus on the device itself. Devices running on lower voltages, devices having intermediate pads between the electrodes and the skin, devices producing pulsating current, and devices having large electrode areas to reduce current concentration all approach the problem from a device perspective. The prior art has not attempted to understand the resistivity of the skin and develop a system that can take advantage of the natural properties of the skin in order to optimize the iontophoretic delivery while minimizing irritation and skin damages.